The EPIPEN4SCHOOLS® program (Mylan Specialty L.P., Canonsburg, PA) provides EpiPen® (epinephrine injection) Auto-Injectors to qualifying public and private US schools. Results of a pilot survey described characteristics of anaphylactic events occurring in an initial set of participating schools during the 2013-2014 school year. This survey was subsequently readministered to large US school districts (≥50 schools per district), which were underrepresented in initial survey findings. Here, data from schools in large districts were added to initial findings in a comprehensive combined analysis. A cross-sectional, web-based pilot survey was distributed to US schools participating in the EpiPen4Schools program. A total of 1140 anaphylactic events were reported among 6574 participating US schools. Status of the affected individual was reported for 1063 events; of these, 89.5% (951/1063) occurred in students, 9.2% (98/1063) occurred in staff members, and 0.8% (8/1063) occurred in visitors. Of the events occurring in students with data on grade level (n=891), 44.9% (400/891) occurred in students in high school, 18.9% (168/891) occurred in students in middle school, and 32.5% (290/891) occurred in students in elementary school. Twenty-five percent of all reported events (262/1049) occurred in individuals with no known allergies. Triggers were reported for 1035 events. Among these, food triggers were most frequent (60.1%, 622/1035); however, triggers were unknown in 21.6% of events (224/1035). The unpredictability of anaphylaxis is highlighted by the frequency of events with unknown triggers (21.6%) and of events occurring in individuals with no known allergies (25.0%). Results underscore the necessity for comprehensive preparedness training in US schools.